Apparatus for separating blood into components thereof

ABSTRACT

Apparatus is disclosed for centrifugally separating blood into a first blood component, such as a plasma-rich component, and a second blood component, such as a plasma-poor component. This apparatus employs a self-balancing centrifuge intended to be used immediately adjacent to a blood donor. The blood pathway is completely disposable and includes a phlebotomy needle and blood compatible tubing connecting the phlebotomy needle to a flexible blood processing bag designed to be supported within a contoured processing chamber in the centrifuge rotor so that second blood component travels along a short internal bag dimension to achieve separation. A displacement chamber having a fluid operated diaphram is also positioned within the blood processing chamber of the centrifuge rotor. Separated first blood component can be expressed from the flexible blood bag by movement of the diaphram and collected in a receiver container as the centrifuge rotor spins. The centrifuge rotor can then be stopped to allow return of second blood component to the donor.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention is in the field of blood processing and more particularlyrelates to the separation of blood, including whole blood, into two ormore components.

2. Description of the Prior Art

Whole human blood includes at least three types of specialized cells.These are the red blood cells, white blood cells and platelets. All ofthese cells are suspended in plasma, a complex aqueous solution ofproteins and other molecular substances.

Until relatively recently, blood transfusions have been given usingwhole blood. There is, however, growing acceptance within the medicalprofession for transfusing only those blood components required by aparticular patient instead of transfusing whole blood. Transfusing onlythose blood components necessary preserves the available supply ofblood, and in many cases, it is better for the patient. Before bloodcomponent transfusions can be widely employed, however, satisfactoryblood separation techniques and apparatus must evolve.

One desirable blood separation is plasmapheresis which is the separationof whole blood into a plasma-rich component and a plasma-poor component.Typically, the plasma-rich component is retained for later use and theplasma-poor component is returned to the donor.

Presently, plasmapheresis is performed on a large scale using satellitepouch systems. A variety of satellite pouch plasmapheresis systems havebeen patented, and some typical examples are those systems described inU.S. Pat. No. 3,190,546 to Raccuglia et al.; U.S. Pat. No. 3,211,368 toShanley; and U.S. Pat. No. 3,545,671 to Ross. With such systems wholeblood is withdrawn from a donor and flows to a pouch containing ananti-coagulant. The pouch is then disconnected from the donor phlebotomyline, centrifuged in a swinging bucket type of centrifuge in which cellsmust travel about half the long dimension of the pouch, typically about12 cm. The centrifuge must then be gently slowed to a stop and the pouchcarefully lifted from the bucket of the centrifuge while avoidingremixing of the two components. The pouch is mounted in a plasmaexpressor and a supernatant plasma fraction is expressed into aconnected plasma pouch, care being given to clamp off the connectingtube between the pouches just before plasma-poor component passes over.The pouch containing the plasma-poor component is then reconnected tothe phlebotomy line so that the plasma-poor component can be returned tothe donor.

It has become customary with satellite pouch systems to carry out thissequence of steps twice for each donor. Typically, one unit, or about500 ml of whole blood is withdrawn, anti-coagulated and separated.Approximately 250 ml of plasma-rich component is obtained and theplasma-poor component is returned to the donor. Subsequently, anotherunit of whole blood is withdrawn and processed in a similar manner.Using such techniques with satellite pouch systems, it often takesapproximately 11/2 hours to obtain 500 ml of separated plasma-richcomponent and to return the plasma-poor component to the donor, eventhough the time for donating a unit of whole blood is only about 20minutes. This relatively long processing time imposes a major limitationon volunteer donor recruitment. Additionally, because the blood pouch isdisconnected from the donor at the end of each withdraw cycle andtransported to and from a separate centrifuge room for centrifugation,there is always the danger of returning blood components to a donorwhich are not his own. Satellite pouch systems require particularlycareful handling of the pouch containing separated plasma-rich andplasma-poor components to avoid remixing thereby ruining the separation.

Blood cell separation systems, both continuous and intermittent flow,have been placed in widespread use but have not been accepted forwidespread application in plasmapheresis because the disposable bloodpathways used are too expensive relative to the satellite pouch systems.An example of a recently developed plasmapheresis apparatus is describedby Latham in U.S. Pat. No. 4,086,924. In this apparatus, whole blood canbe withdrawn from a donor using a phlebotomy needle and pressure cuff.The whole blood is anti-coagulated and transported by a blood pump to aplasmapheresis centrifuge where it is separated into plasma-rich andplasma-poor components. Separated plasma-rich component is stored in aplasma container. When a predetermined quantity of separated plasma-richcomponent has been obtained, cycle control means immediately switch fromthe withdraw cycle to a return cycle. The cycle control means alsoimmediately switch from the return cycle to either a withdraw cycle or astandby cycle in response to a signal from monitoring means indicatingthat the return of plasma-poor component has been completed. Themanufacturing costs of the disposable blood pathway for this system hasbeen greater than that for a satellite pouch system, however, andalthough the Latham system is attractive because of the short (30 min.)donor time required, it has involved too much expense to be accepted foruse on a wide scale.

One main reason for the relatively high expense of the disposable bloodpathway in prior blood separation systems of the Latham type relates tothe requirement for a specially manufactured blood centrifuge bowl. Manytimes, for example, parts for these are injection molded from relativelyexpensive materials, such as polycarbonate, which adds a major elementof expense to the disposable blood pathway. Another reason for therelatively high expense in the Latham system is the requirement forprecisely manufactured rotary seals to pass blood in and plasma-richcomponent out of the centrifuge bowl as it is spinning. It istheoretically possible to eliminate such inordinate expense, therefore,by employing a relatively inexpensive, disposable blood bag as theprocessing chamber and by eliminating the requirement for a rotary seal.Blood separation systems have been designed with one or both of these inmind, but such systems have invariably suffered from their own set ofproblems and disadvantages.

Mitchell et al., in U.S. Pat. No. 3,674,197, for example, point out someproblems encountered with attempts to use standard flexible blood bagsin a centrifuge rotor. The problems mentioned relate to the necessity toproperly support the liquid filled bags because they are subjected tovarious pressures and forces during centrifugation which are not evenlydistributed. The shifting of position of the flexible blood bags causeswrinkles and folds in the bag material with consequent imbalancing ofthe rotor. The Mitchell et al. invention disclosed in this patentrelates to contoured shoes which surround a cylindrical flexible bloodprocessing bag to alleviate such problems. However, there is no attemptby these patentees to provide a contoured blood processing chamber whichsupports a standard blood bag in a position to achieve centrifugalseparation by minimizing the distance that the blood components arerequired to travel during centrifugation.

Another approach to using a flexible blood processing bag in acentrifugation system is disclosed by Jones et al. in U.S. Pat. No.3,737,096. The highly specialized system disclosed therein is a cellwashing system in which a flexible blood bag receives fluid and hasfluid withdrawn from it during operation of the centrifuge. The volumeof the processing chamber in this centrifuge is adjusted by a flexiblemembrane connected to a displacement fluid which expands or contracts,respectively, in reponse to introduction of or withdrawal of adisplacement fluid. This system has the disadvantage of requiring arotary seal. Additionally, the flexible bag is relatively complex anddoes not have a design intended to minimize the distance which bloodcomponents travel during separation.

As can be appreciated from the above discussion, there has been veryconsiderable effort applied to developing new blood processing systems.Despite this, none of the systems developed heretofore provide thecombination of inexpensive disposable blood processing sets, rapidseparation, ease of making a fine cut between different blood componentsand the capability to carry out the entire blood processing immediatelyadjacent to a blood donor.

SUMMARY OF THE INVENTION

The invention comprises an apparatus for separating blood, includingwhole blood, into a first blood component and a second blood component.

A self-balancing cengtrifuge having a rotor capable of spinning atspeeds sufficient to effect the desired separation in a relatively shortperiod of time without significant concomitant vibration is employed. Aself-balancing centrifuge is employed because unbalanced masses of bloodcomponents and displacer fluid are introduced or withdrawn duringprocessing which would render a conventional centrifuge useless forseparation. Such a self-balancing centrifuge allows operation over wideranges of rotating speeds and levels of unbalance so that it can beapplied to various clinical procedures where the rotating speeds andtheir corresponding separation forces are variable.

A flexible, disposable blood processing bag is mounted in a contouredprocessing chamber within the centrifuge rotor. The contoured chamber isdesigned to support the blood bag in a position whereby second bloodcomponent traverses a short distance in the process of separation. Aflexible diaphram is also positioned in the blood processing chamber ofthe rotor in a complementary relationship to the flexible disposableblood bag. The flexible diaphram can be moved to apply pressure to thedisposable blood bag in response to the introduction or expulsion,respectively, of a displacement fluid while the centrifuge rotor iseither rotating or stationary. Additionally, displacer fluid can beexpelled by pumping blood into the flexible, disposable blood processingbag.

During separation, displacement fluid is introduced into thedisplacement chamber to drive the diaphram so that separated firstcomponent is expelled into a receiver container. Preferably, thisreceiver container is also positioned within the centrifuge rotor.

After separation of a desired amount of first blood compenent, the rotoris stopped and any changes in the blood pathway required for return ofsecond blood component are made. Second blood component can then bereturned by introducing more displacement fluid into the displacementchamber. After second component has been returned, additional blood tobe separated can be introduced into the flexible blood processing bagthereby forcing displacement fluid from the displacement chamber. Theseparation procedures can then be repeated.

The apparatus described herein employs a completely disposable,relatively inexpensive blood pathway set, including the blood processingbag. The apparatus is extremely versatile and can be used in a greatmany applications where it is desirable to separate one or morecomponents from blood, including separations requiring precise cutsbetween centrifugally separated fractions. Additionally, theseseparations can be done quickly with the apparatus stationed next to ablood donor since it can be made quite small and light in weight. Thisapparatus also provides the capability of separating blood cells withoutsubjecting them to the trauma associated with intense mechanical shearexperienced in conventional rotary seal machines and in the morerecently developed machines which eliminate the need for a rotary sealby employing a rapidly flexing umbilical cable to pass fluids to andfrom a centrifuge rotor. The ease with which the operating techniciancan observe progress of the separation process and the accuracy ofcontrolling making product cuts is also an advantage. Additionally,there is less platelet activation, less particulate contaminationpossible, and less anti-coagulant required with this apparatus.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic illustration of an apparatus according to thisinvention which is suitable for plasmapheresis;

FIG. 2 is a diagrammatic view of the disposable blood pathway suitablefor use in the apparatus of FIG. 1;

FIG. 3 is a perspective view of a flexible, disposable, blood processingbag suitable for use in the apparatus of FIG. 1;

FIG. 4 is a perspective view of a flexible fluid bag suitable for use asa displacement pouch in the apparatus of FIG. 1;

FIG. 5 is a perspective view of complementary support shoes for theblood processing bag and displacement pouch of FIGS. 3 and 4,respectively;

FIG. 6 is a perspective view of a holder for the support shoes of FIG.5;

FIG. 7 is a partially cut-away front elevational view of aself-balancing centrifuge suitable for use in the apparatus of FIG. 1;

FIG. 8 is a plan view of the centrifuge of FIG. 7;

FIG. 9 is a partially cut-away side elevational view of the centrifugerotor with a portion of the disposable blood pathway shown in FIG. 2contained therein; and,

FIG. 10 is a partially cut-away side elevational view of a centrifugerotor containing a blood processing bag having an alternative geometrytogether with a complementary displacement bag and a receiver container.

DESCRIPTION OF PREFERRED EMBODIMENTS

As used herein, the following terms are defined to mean:

"Self-balancing" centrifuge--a centrifuge which is designed so that oncethe rotor has surpassed a minimum in rotational velocity, the rotor willspin around its angular momentum vector rather than its geometrical axisof symmetry. Thus, disruptive vibrations from an unbalanced rotor, whichwould create intolerable vibrations in a conventional centrifuge, arenot generated.

"First blood component"--one fraction of blood which it is desired toseparate from another fraction;

"Second blood component"--another fraction separated from blood which isthe balance after first blood component has been separated therefrom;

"Plasma-rich component"--a fraction of blood which is richer in plasmathan whole blood;

"Plasma-poor component"--a fraction of blood which is poorer in plasmathan whole blood.

The preferred embodiments of this invention can now be further describedwith specific reference to the Figures.

A plasmapheresis separation can be illustrated with reference to FIG. 1,which is a diagrammatic illustration of plasmapheresis apparatus 10, andFIGS. 2-9, which illustrate components of the plasmapheresis apparatus10 in more detail.

To withdraw whole blood from donor's arm 12, a standard phelbotomyneedle 16 can be used with this apparatus. Phlebotomy needle 16 mightbe, for example, a 15-gauge, thin wall phlebotomy needle of the typewhich has a supply of anti-coagulant connected to it so that freshlywithdrawn blood is anti-coagulated as soon as it leaves the needle. Aparticularly suitable phlebotomy needle of this type is described indetail in U.S. Pat. No. 3,916,892 issued to Latham.

Anti-coagulant is supplied from anti-coagulant pouch 18 to phlebotomyneedle 16 through anti-coagulant tubing 20 which is connected throughtransparent drip chamber 22 and spike 23 to pouch 18. Transparent dripchamber 22 allows the operator to observe anti-coagulant flow. Pump 24provides anti-coagulant pumping, when necessary, and is a roller-typepump having a movable platen 26 which is employed to clamp blood tubing20 against rollers 25. Roller pumps of this type are described in detailin U.S. Pat. No. 3,565,286, also issued to Latham.

Prior to making the venipuncture, the disposable set of software ismounted in the permanent components of apparatus 10. Anticoagulant pouch18 is connected by insertion of spike 23 in the conventional mannerwhile pump platen 26 is clamped against tubing 20. Drip chamber 22 issqueezed slightly to expel some of its contained air into anticoagulantpouch 18 and then released so that a small pool of anticoagulantaccumulates in the lower portion of drip chamber 22.

Blood processing bag 50 is completely collapsed by passing as muchdisplacer fluid into pouch 69 as possible. Clamp 142 (FIG. 8) is thenclosed to isolate blood processing bag 50 from component receivercontainer 61.

Anticoagulant tubing 20 and blood tubing 28 are primed withanticoagulant by releasing pump platen 26 to allow gravity flow ofanticoagulant through these lines until a small quantity collects inmonitor pouch 30. Pump platen 26 is then reclamped. Throughout thispriming procedure the small pool of anticoagulant in the lower sectionof drip chamber 22 serves to prevent entrainment of air bubbles in thestream of anticoagulant entering tubing 20 thereby assuring an air-freeprimed condition. Also, the operator is able to visualize the rate ofanticoagulant flow through the air space in the upper portion of dripchamber 22 and thereby verify that approximately the correctanticoagulant flow is occuring at all times.

The site where the venipuncture is to be made is then prepared. Afterpreparation, pressure cuff 27 is fastened around donor's arm 12 at alocation above where phlebotomy needle 16 is to be inserted.Pressurizing gas is supplied to pressure cuff 27 from a gas canister(not shown), and the precise pressure applied is usually regulated by apressure regulator. A gas valve may also be provided which has an openand a relief position, the latter being provided to release pressure inpressure cuff 27. A typical pressure is about 50 mm Hg which raises thepressure in the donor's veins sufficiently to facilitate thevenipuncture and to boost blood flow from the donor's veins.

Plasmapheresis apparatus 10 is now started by energizing electricalsystems to control pump motors, activate detectors, control pressurecuff 27, etc. Control logic may be used to monitor and control theoverall operation of the plasmapheresis apparatus, if desired.

The venipuncture is them made by inserting phlebotomy needle 16 into avein in donor's arm 12 at the previously prepared site. Freshlywithdrawn, anti-coagulated, whole blood flows under venipressure fromthe donor through blood-compatible tubing 28 into monitor pouch 30.Monitor pouch 30 can have either a weight detector 32 or a pressuredetector 34 associated with it, or both. Weight detection can be used tosense the weight of blood which is present in the monitor pouch at anygiven time. This in turn can be used to both activate and control thespeed of blood pump 36, which is also a roller-type pump having rollers37 and a movable platen 38. The function of pressure detector 34 will bedescribed in conjunction with the return cycle.

At the start of a withdraw cycle, monitor pouch 30 is empty insofar asblood and blood components are concerned. As blood enters monitor pouch30, its weight eventually reaches a threshold value which is sensed byweight detector 32. At this threshold weight, an appropriate signal istransmitted to actuate rollers 37 in blood pump 38 and to actuaterollers 25 in anti-coagulant pump 24. Blood pump 38 preferably has atleast two speeds, and these speeds are determined by speed controller 39acting in response to the signals received from weight detector 32. Ifthe blood flow from phlebotomy needle 16 is greater than that to bloodpump 36, monitor pouch 30 fills thereby becoming heavier and causingweight detector 32 to transmit signals to speed controller 39 to advanceblood pump 36 to a higher speed position. If, on the other hand, bloodflow from phlebotomy needle 16 is less than that to blood pump 36,monitor pouch 30 begins to empty thereby losing weight and causingsignals to be transmitted to speed controller 39 to return pump 36 to alower speed position. If monitor pouch 30 continues to lose weight evenat the lower pump speed, a signal can likewise be transmitted to causeblood pump 36 to operate at a still lower speed, if available, or to beshut off entirely until monitor pouch 30 fills once again. In this way,blood is pumped from monitor pouch 30 but never from the donor. Thispattern of action continues through a withdraw cycle.

Anti-coagulated whole blood is pumped from monitor pouch 30 throughblood compatible tubing 41 to a first U-shaped flow divider 42 havinglegs 43 and 44 (FIG. 2). Leg 44 is connected by tubing 45 to a spikeport 46, but flow is prevented along this path at this time by clamp 47which is closed. Whole blood does flow through leg 43 andblood-compatible tubing 48 to second U-shaped flow divider 42' havinglegs 43' and 44'. Leg 44' is connected by blood compatible tubing 45' toa spike port 46'. Tubing 45' is clamped off at this point in theprocedure by clamp 47' so that anti-coagulated whole blood flows alongleg 43' and tubing 49 to blood processing bag 50.

Blood processing bag 50 can be seen in more detail in FIG. 3. Therein,it can be seen that flexible, disposable blood processing bag 50 has afront, planar, generally-rectangular panel 52. There is also a matchingplanar, generally-rectangular back panel, which cannot be seen, and thefront and back panels are sealed together around the periphery 54 of bag50 with a fluid-tight seal. A pattern of holes 55 is provided in sealedperiphery 54 to help in registering blood processing bag 50 in itsproper location within contoured shoes which are described below.

Blood processing bag 50 has three fluid ports, 56, 57 and 58, located atits top, and a fluid port 59 located approximately in the center offront panel 52. Blood-compatible tubing 60 extends from port 59 and isconnected to receiver container 61 at entry port 62. The receivercontainer 61 can be a blow-molded container formed as a volume ofrevolution with its upper and larger than its lower end. Inlet port 62is located at a point of substantially maximum diameter of receivercontainer 61 so that material can be withdrawn from container 61 backinto blood processing pouch 50, if desired. Receiver container 61 isalso provided with top flaps 63 and 64 and bottom flap 65, each havingholes therein, so that container 61 can be conveniently hung from itstop or bottom. Of course, these flaps are optional and may be omitted orreplaced with spike ports, etc. Receiver container 61 additionally has asterile air filter 67 which allows any air contained within the systemto pass therethrough. Other receiver container geometries can beemployed, of course, with any geometry designed to minimize rotorimbalance as first blood component is introduced being preferred.

FIG. 4 illustrates a flexible displacement pouch 69 which serves as adisplacement chamber in plasmapheresis apparatus 10. Flexible,displacement pouch 69 is a flexible liquid bag formed from planar frontand back panels and having a peripheral seal 70. Registration holes 71are provided in the peripheral seal 70 and a single inlet/outlet port 72is provided at the bottom to allow displacer fluid to be transportedinto or out of pouch 69 via displacer fluid tubing 73.

Blood processing bag 50 and flexible displacement pouch 69 are held in acomplementary relationship in a contoured processing chamber formedbetween a pair of support shoes which are shown in FIG. 5.

Shoe 74 has an inner surface 75 having a generally cylindrical shapeapproximately concentric with the geometrical axis of rotation. Innersurface 75 contacts the radially outward face of pouch 69 duringprocessing. Channel 76 is provided in shoe 74 to allow displacer fluidtubing 73 to pass through the support shoes when they are held in theirclosed position. A pattern of pegs 77 is provided around the edge ofsupport shoe 74, and the function of pegs 77 is described below.

Support shoe 78 is actually split into upper shoe half 78a and lowershoe half 78b, to allow tubing 60 to be inserted through hole 79 of shoe78. This is necessary because the entire blood pathway, as illustratedin FIG. 2, is integral and disposable. Peg holes 80 are provided aroundthe inner edge of shoe 78 to accommodate pegs 77 located around theinner edge of support shoe 74.

Inner surface 81 of shoe 78 has a somewhat cylindrical contour, but isadditionally contoured to have a gentle slope from both its top andbottom towards a horizontal center line passing through hole 79 and isalso contoured to have a gentle slope from both sides towards a verticlecenter line passing through hole 79. Such contoured sloping provides acentrifugal slope from all points so that separated first bloodcomponent is always directed towards outlet 59 of blood processing pouch50 during centrifugation.

Channels 82, 83 and 84 provide access to the contoured processingchamber formed between shoes 74 and 78 when they are positionedtogether. Channels 82, 83 and 84 can be used therefore to pass tubing45, 45' and 49 into the contoured processing chamber formed betweensupport shoes 74 and 78 or to accommodate connections to tubing 45, 45'and 49.

Support shoes 74 and 78 can be formed from polymers such as foamedpolyurethane. In some cases, it will be preferred to have transparentsupport shoes, in which case they can be formed from transparentpolymers, such as poly(methyl methacrylate). Many other materials couldbe used in forming these support shoes, or course.

Pouch 69 is mounted on shoe 74 by inserting pegs 77 through registrationholes 71 in the peripheral seal 70 of pouch 69; subsequently, processingbag 50 is mounted on pegs 77 in the same manner employing registrationholes 55 while insuring that its port 59 is positioned radiallyinwardly. Shoes 74 and 78 are then closed together so that pegs 77extend into matching holes 80 in the edge of shoe 78. In their closedposition, shoes 74 and 78 form an enclosed contoured processing chambercontaining blood processing bag 50 and fluid displacer pouch 69, whichare positioned so that their contacting planar panels assume acomplementary relationship.

When blood processing bag 50 and flexible pouch 69 are positioned inthis complementary relationship within the contoured processing chamberformed between support shoes 74 and 78, pouch 69 serves as adisplacement chamber having a fluid-actuated diaphram. As displacerfluid is introduced into pouch 69, it expands to force blood or bloodcomponents out of processing bag 50. Similarly, as anti-coagulated wholeblood passes into blood processing bag 50 under positive pressure, anequal volume of displacer fluid is forced from the flexible displacementpouch 69.

The basic shape of the contoured processing chamber is an arc of acylindrical annulus approximately concentric with the axis of rotation.The radial thickness of this chamber is minimized, and is preferablyless than 15% of the peripheral length of the arc. The contour of thewall of the chamber on the side nearest the axis of rotation is modifiedfrom a true arc about this axis to provide a slope for natural drainagewithin the centrifugal field of the less dense plasma-rich componenttoward outlet port 59 located in the center of the radially inner faceof blood processing bag 50. This is achieved by the centrifugal slopeprovided by the contoured surface 81 of support shoe 78.

Support shoes 74 and 78 are held in a closed position by placing them ina support shoe holder 85 illustrated in FIG. 6. Holder 85 has acylindrically shaped back wall 86, two side walls, 87 and 88, each ofwhich has a curved lip 89 at its terminal portion which curls around tocontain support shoes 74 and 78. Holder 85 is also provided with ahandle 90 so that it can be conveniently lifted. Support shoe holder 85can be formed from materials such as aluminum, etc.

A plasmapheresis procedure employing apparatus 10 is as follows. Priorto withdrawing blood from donor's arm 12, blood processing bag 50 iscollapsed by filling pouch 69 completely with displacer fluid while tube60 is tightly clamped. The displacer fluid distends bag 69, which inturn compresses processing bag 50 against inner surface 81 of shoe 78 toexpress any blood or blood components from bag 50.

Use of a fixed charge of displacer fluid passing in tubing 92 between astationary displacer fluid station 93, external to centrifuge rotor 94,and displacer pouch 69 within rotor 94, allows the monitoring of thevolume of blood introduced into blood processing bag 50 since the totalvolume of the displacer pouch and blood processing bag is constant.Thus, the amount of blood or components in blood processing bag 50 canbe accurately determined by monitoring either changes in weight orvolume of displacement fluid in displacer station 93.

When the desired amount of whole blood has been withdrawn from a donor,blood compatible tubing 49 is first sealed, such as can be done with adielectric sealer, and then cut. This is typically done by sealingtubing 49 in two places and by cutting between the seals or by making abroad seal which is cut in the middle. Anti-coagulant pump 24 continuesto slowly pump anti-coagulant through phlebotomy needle 16 at this pointto prevent clot formation therein while blood is not flowing.

Centrifuge motor 102 is now activated to cause centrifuge rotor 94 torotate at a speed sufficient to separate the withdrawn whole bloodcontained in processing bag 50 into a plasma-rich component and aplasma-poor component. A typical rotor speed, for example, might beabout 4800 rpm.

As centrifuge rotor 94 rotates, plasma-poor component, which in thiscase consists primarily of red blood cells, white blood cells andplatelets, moves towards the radially outer face of disposable bloodprocessing bag 50. This creates plasma-rich component near the radiallyinner face, and this can be expressed from disposable processing bag 50as centrifuge rotor 94 spins by introducing displacer fluid intodisplacement pouch 69 thereby applying pressure to disposable bloodprocessing bag 50. Plasma-rich component is expressed through centralport 59 of the flexible blood processing bag 50 and is transported intubing 60 to receiver container 61 as rotor 94 continues spinning andfurther separation. Tubing 60 is preferably kept relatively short toprevent it from folding back upon itself when the software is positionedin the centrifuge rotor.

Whenever plasma-rich component is being expressed from blood processingbag 50, tube clamp 142 (FIG. 8) is released to permit flow throughtubing 60 to receiver container 61. At all other times, clamp 142 iskept closed. Since the inlet for receiver container 61 is positioned ata point of maximum diameter, it is possible to withdraw material fromreceiver container 61 back into blood processing pouch 50 by withdrawingdisplacer fluid from displacement pouch 69 while clamp 142 is open. Thisoperates as a safeguard in case material is expressed from bloodprocessing pouch 50 beyond that where the cut is desired. An opticaldetector can be provided, if desired, to sense when the separation hasbeen completed. Clamp 142 is hydraulically operated by fluid containedin hydraulic fluid reservoir 95 and supplied in line 97.

When the cut has been completed, centrifuge rotor 94 is braked to astop. A protective cover, if present, is removed from bag spike 46' andalso from spike port 56 in blood processing bag 50. Slide clamp 47' onbag spike 46' is opened just long enough to allow spike 46' to primewith blood from blood tubing 45'. At this point, spike 46' is insertedinto spike port 56 at the top of flexible, disposable blood processingbag 50 and slide clamp 47' is fully opened.

Plasma-poor component can now be returned to the donor by opening bloodpump platen 38, and introducing displacer fluid into displacement pouch69. Displacer fluid is transported to pouch 69 until it is once againfilled with displacer fluid indicating that all of the plasma-poorcomponent has been returned to the donor. This can be determined bymeasuring the amount of displacer fluid transported from stationarydisplacement station 93.

In the return cycle, monitor pouch 30 fills with plasma-poor component.Pressure detector 34 senses any undesirable build-ups of pressure in thesystem, which might be caused, for example, by a restriction at the tipof phlebotomy needle 16. When such a build-up is sensed, an appropriatesignal can be transmitted to slow or halt the transport of displacerfluid to pouch 69. Optionally, an audible or visual alarm may be given.

When the plasma-poor component has been returned to the donor, a secondwhole blood withdrawal can be initiated. This can be done similarly tothe first withdrawal cycle, except that the whole blood now flowsthrough spike port 46' and into the top of disposable, flexible bloodprocessing pouch 50 through port 56. After the desired amount ofanti-coagulated whole blood has been introduced into disposable,flexible blood processing bag 50, blood compatible tubing 45' is sealedand cut, as before. Processing can now commence in a manner similar tothat previously described.

At the end of the separation, centrifuge rotor 94 is stopped, theprotective covers from bag spike 46 and spike port 58 are removed, slideclamp 47 is opened just long enough to allow spike 46 to prime withblood, and then spike 46 is inserted into spike port 58. Slide clamp 47is fully opened and plasma-poor component remaining in flexible,disposable blood processing pouch 50 is returned to the donor, asbefore.

In a typical plasmapheresis separation as described, 500 ml of wholeblood can be withdrawn in each withdrawal cycle. Each centrifuge cyclecan produce about 250 ml of plasma-rich component having a small amountof anti-coagulant therein. This plasma-rich component is essentiallyfree of other components. The plasma-poor component can be returned tothe donor and would typiclly consist of something like about 84% redblood cells, 1% platelets and about 15% plasma--it would also contain asmall amount of anti-coagulant. Thus, after two withdraw cycles of 500ml of whole blood each, and two separation and return cycles,approximately 500 ml of plasma remain in the plasma receiver. The timefor carrying out the entire procedure is likely to be thirty minutes orless.

Unbalance in centrifuge rotor 94 is minimized, even though fluid isbeing introduced and withdrawn during its operation, since the totalvolume of fluid, within the assymetric portion of the fluid pathway,namely blood plus displacer fluid, remains constant. To further minimizeunbalance, it is preferable to employ displacer fluid having a densityclose to that of whole blood, such as within ±15% of the density ofwhole blood. It is further preferred, if displacer pouch 69 is locatedradially outwardly, to employ displacer fluid having a density greaterthan that of the second blood component--this helps to maintain agenerally cylindrical interface between the displacer pouch 69 andblood-processing bag 50 and minimizes any tendency for the processingbag 50 to be pinched off during return of second blood component to adonor. As an example, in a plasmapheresis separation, a displacer fluiddensity of about 1.1 would be suitable since typical specific densitiesfor whole blood, packed cells and plasma are approximately 1.06, 1.09and 1.05, respectively. On the other hand, it might be desirable in somecases to locate the displacement pouch on the radially inner side of ablood processing bag, in which case it would be preferred to employdisplacer fluid with a density lower than the lightest blood componentformed during separation.

The shape of receiver container 61 and its positioning within rotor 94also minimize imbalance in the centrifuge. As can be seen, fluid presentin receiver container 61 while rotor 94 is spinning is evenlydistributed about the axis of rotation. Other receiving containers for aseparated blood component can be used, of course, but it is preferableto employ one or more receiver containers which attain a substantiallyeven distribution of fluid therein about the axis of rotation.

It is preferable to employ blood-compatible materials for all tubing,pouches, bags, etc., in this apparatus if they come into contact withblood or a component thereof. An example of such a material ispolyethylene. In some cases, such as those where tubing is cut andsealed, it is particularly preferred to employ a blood-compatible,heat-sealable material, such as poly(vinyl chloride). It is alsopreferable, in many cases, to form pouches and bags from transparentmaterials to permit visibility during processing.

One self-balancing centrifuge suitable for use in the inventiondescribed herein is illustrated in more detail in FIGS. 7-9. Therein,centrifuge 100 can be driven by a standard electric motor 102, which maybe fixed or variable speed. Preferably, motor 102 is vibration isolatedand mounted to a rigid structure through mounting plate 103. Drive pully104, attached to motor drive shaft 105, drives centrifuge drive pully106 via drive belt 107.

A pivot mount is positioned in the plane of pulleys 104, 106 and belt107 to eliminate significant turning moments in planes coincident withthe axis of rotation. A suitable pivot mount can be formed from anelastomeric ring 110 of soft silicone rubber or other similar materialmounted within an outer metallic ring member 111 attached to stationarymount 113 and an inner metallic ring member 115 attached to stationaryhousing 117. This pivot mount allows centrifuge 100 to find its owncenter of rotation around its angular momentum vector, while stillproviding some resistance to undesired movement of centrifuge shaft 112.

The bottom end of centrifuge shaft 112 is journaled in radial ballbearings 114. Shaft 112 is a thin walled tube with good stiffness butone which is light in weight, such as can be formed from stainless steeltubing. Rotary seals 116 and 118 provide communication betweenstationary metallic fluid lines 92 and 97 and internal flexible tubing134 and 144, respectively, the functions of which are described below.

An oiled porous bearing 120 acts as a damped, resilient retraining mountemployed near the top of shaft 112 to provide a slight righting force.Bearing 120 is formed by inner ring member 123 and outer ring member 125with spongy elastomer material 124 therebetween. Outer ring member 125is rigidly secured to support 122. Elastomeric material 124 acts as alight spring and damper, and allows the spring constant and dampening tobe independently controlled. Open cell elastomeric foam is preferred.

Receiver container 61 is located within centrifuge rotor 94 in taperedconical holder 126. Rotor 94 can be formed from aluminum and may beprovided with a protective polymethyl methacrylate guard. Access torotor 94 is conveniently provided through its top.

An optical slit (not shown) positioned directly beneath tubing 60 and astrong projection lamp secured in a stationary location under rotor 94may be used to provide synchronized illumination of tubing 60.Alternately, a sychronized stroboscopic light may be used to illuminatethe entire interior of rotor 94.

Displacer fluid at station 93 can be stored in a transparent graduatedreservoir 130 which facilitates measurements of the amount present. Itis transported to displacer pouch 69 in metal tubing 92 and flexibletubing 134 which are coupled at rotary seal 116. Flexible tubing 134runs up through shaft 112 to displacement pouch 69. Displacer fluid pump136 is used to transport displacer fluid from reservoir 130 to displacerpouch 69. The return of displacer fluid is acheived by inactivating pump136 and opening solenoid valve 140 in by-pass line 138 whereby bloodfilling bag 50 operates to force displacer fluid from pouch 69 and backto reservoir 130 through lines 134, 92 and 138.

Hydraulically actuated clamp 142 is connected by flexible tubing 144 andrigid tubing 94, coupled through rotary seal 118, to hydraulic fluidcylinder 148. Hydraulic pressure is applied by piston 150 which can beoperated in the forward direction by solenoid 152 and in the returndirection by spring 154.

FIG. 9 illustrates blood components as they might occur in an on-goingplasmapheresis cycle. Processing bag 50 contains plasma-poor component,which would typically be packed red cells, indicated by dark stippling,toward its outer radial portion. Plasma-rich component is locatedradially inwardly and is indicated by light stippling. The plasma-richcomponent is also shown in tubing 60 and receiver container 61 as itwould appear towards the end of a plasmapheresis cycle.

Plasma-rich component is expressed from processing bag 50 into receivercontainer 61 by the action of displacement bag 69 which is partly filledwith displacer fluid and has a surface contacting bag 50 so that thissurface acts as a fluid-operated diaphram. Receiver container 61 isprovided with a sterile air filter 67 on its top cover to allow any airpresent in the system to escape.

FIG. 10 illustrates an alternative embodiment in which flexible,disposable blood processing bag 150 is supported by contoured shoe 152so that bag 150 has an inner surface having a slightly greater slope atits upper portion than at its lower portion. This increased slopeprovides more efficient emptying during operation. Displacer pouch 154is contoured into a complementary shape by support shoe 156. Otherelements are the same as previously described. This embodiment permitsuse of tubing 158, connecting bag 150 to receiver container 61, at thetop of bag 150. Thus, support shoe 152 does not have to be split.Displacer pouch 154 can be permanently mounted, if desired, in this orpreviously described embodiments.

Those skilled in the art will recognize many equivalents to the specificembodiments described herein. Such equivalents are considered part ofthis invention and are intended to be covered by the following claims.

What is claimed is:
 1. Apparatus for separating blood into a first blood component and a second blood component, comprising, in combination:a. a self-balancing centrifuge having a rotor capable of rotating at relatively high speeds sufficient to effect the desired separation in a short period of time without significant concomitant vibration, said rotor having a blood processing chamber therein containing a flexible-disposable blood processing bag having inner and outer wall members with a relatively small distance between said inner and said outer wall members compared to other internal bag dimensions, said processing chamber being contoured to support said flexible, disposable blood processing bag in a positon so that the short internal bag dimension is positioned transverse to the axis of rotation whereby second blood component travels along said relatively short internal bag dimension during centrifugal separation thereof; b. means for introducing blood to be separated into said flexible, disposable blood processing bag; c. means for rotating said centrifuge rotor at said relatively high rotational speeds to effect separation of said first and said second blood components; d. a displacement container having a fluid-operated flexible diaphragm, said displacement container being positioned in the processing chamber complementary to said flexible, disposable blood processing bag whereby the fluid-operated diaphragm is positioned to exert pressure on said blood processing bag as fluid is introduced into said displacement container to expel first blood component from the blood processing bag; e. a receiver container for receiving first blood component expelled from said flexible, disposable blood processing bag, said receiver container being located within said centrifuge rotor and having a geometry which minimizes rotor imbalance as first blood component is introduced therein; f. blood compatible tubing connecting said blood processing bag to said receiver container; and g. means for introducing displacer fluid into said displacement container as said centrifuge rotor is rotating thereby providing for the fluid-operated flexible diaphragm to exert pressure on said flexible, disposable blood processing bag to expel first blood component from said disposable blood processing bag into said receiver container.
 2. An apparatus of claim 1 wherein said receiver container for receiving first blood component comprises a disposable receiver container formed as a volume of revolution with its upper end larger than its lower end, said receiver container being positioned in said centrifuge rotor so that its axis of rotation is substantially coincident with the axis of rotation of said rotor and having a first blood component inlet at a point of substantially maximum diameter of said receiver container.
 3. An apparatus of claim 2 wherein said means for introducing blood to be separated comprises means for withdrawing whole blood from a donor.
 4. An apparatus of claim 3 additionally including:means for halting rotation of said centrifuge rotor; means for clamping the blood-compatible tubing connecting said blood-processing bag to said receiver container; and, means for reconnecting said blood processing bag to said donor.
 5. An apparatus of claim 4 wherein said blood processing chamber is defined by complementary contoured support shoes.
 6. An apparatus of claim 5 additionally including means for monitoring the amount of displacer fluid present in said displacement container.
 7. An apparatus of claim 6 additionally including optical means for providing visibility of the separation.
 8. An apparatus of claim 7 wherein said diaphram is positioned radially outward from said blood bag, said displacer fluid has a density greater than that of said second blood component, said displacer fluid enters the displacement chamber from the bottom, and said second blood component is returned through a port at the top of said blood bag.
 9. An apparatus of claim 7 wherein said diaphram is positioned radially inwardly from said blood bag and said displacer fluid has a density less than that of a second blood component.
 10. In a method of processing blood including centrifugally separating blood into a first blood component and a second blood component within a flexible blood processing bag located within the rotor of a blood processing centrifuge and subsequently expelling first blood component from said flexible blood processing bag with a flexible diaphragm positioned complementary to said blood processing bag and radially outward therefrom and driven by displacer fluid:the improvement of employing a displacer fluid having a density greater than the density of said second blood component.
 11. In a method of processing blood including centrifugally separating blood into a first blood component and a second blood component within a flexible blood processing bag located within the rotor of a blood processing centrifuge and subsequently expelling first blood component from said flexible blood processing bag with a flexible diaphragm positioned complementary to said blood processing bag and radially inward therefrom and driven by displacer fluid:the improvement of employing a displacer fluid having a density of less than the density of said first blood component.
 12. A centrifuge system for separating blood into a first blood component and a second blood component within a flexible blood processing bag and subsequently expelling first blood component from the flexible bag by employing a fluid-operated diaphragm to apply pressure to said blood processing bag, comprising, in combination:a. A centrifuge rotor having a contoured processing chamber formed between complementary support shoes contoured to support the flexible blood processing bag and fluid-operated diaphragm in a complementary relationship in which said second blood component is required to travel along a relatively short dimension of said flexible blood processing bag during centrifugal separation thereof; b. an elongated, thin-walled tubular rotor shaft extending downwardly from said centrifuge rotor; c. means for pivotally mounting said rotor shaft at its bottom; d. means for providing a clamped, resilient, restraining mount to a support member toward the top of said shaft, whereby said centrifuge rotor can rotate about its angular momentum vector; e. means for driving said rotor shaft; f. a reservoir containing displacement fluid located external to said centrifuge rotor; g. means for transmitting displacement fluid between said reservoir and said fluidoperated diaphragm in the processing chamber of said centrifuge rotor whereby separated first blood component can be expelled from the blood processing bag; and, h. means to receive separated first blood component expelled from said blood processing bag.
 13. A centrifuge system of claim 12 wherein said means for driving said rotor shaft comprise a motor driven drive pulley connected to a driven pulley on said shaft by a drive belt.
 14. A centrifuge system of claim 13 wherein said means for pivotally mounting said rotor shaft include a pivot mount positioned in the plane of said drive pulley and said driven pulley, said pivot mount comprising an inner ring member and an outer ring member independently mounted with respect to each other and containing therebetween an annularly shaped ring of compressible material.
 15. A centrifuge system of claim 14 wherein said compressible material is a soft elastomeric material.
 16. A centrifuge system of claim 15 additionally including clamping means in said centrifuge rotor for limiting the amount of first blood component expelled from said blood processing bag and into said means to receive separated first blood component and means for actuating said clamping means.
 17. A centrifuge system of claim 16 additionally including first rotary seal means for coupling a displacer fluid supply line to displacer tubing contained within said rotor shaft.
 18. A centrifuge system of claim 17 wherein said clamping means comprises a hydraulically-actuated clamp and additionally including second rotary seal means for coupling a hydraulic fluid supply line to tubing contained within said rotor shaft and leading to said hydraulically-actuated clamp.
 19. A method of centrifugally separating blood contained within a flexible blood processing bag into a first blood component and a second blood component, comprising:a. mounting said blood processing bag in a centrifuge rotor in a position so that said second blood component will be forced radially outward during centrifugal separation for a distance corresponding to a short internal bag dimension; b. rotating said centrifuge rotor at a speed sufficient to cause said second blood component to travel radially outwards along the short internal bag dimension thereby causing first blood component to collect near the radially inner surface of said bag; and, c. partially collapsing said blood-processing bag by applying pressure to an external surface thereof to thereby expel first blood component from said blood processing bag and into a receiver container within said centrifuge rotor.
 20. A method of claim 19 wherein said blood processing bag has substantially planar front and back panels sealed together at their edges and is mounted in a position within said centrifuge rotor wherein the radial distance which second blood component travels is substantially equal to the distance between the front and back planar panels of said bag.
 21. A method of claim 20 wherein said first blood component is expelled by applying pressure to the radially inner surface of said blood processing bag.
 22. A method of claim 19, 20 or 21 wherein said first blood component comprises a plasma-rich component and said second blood component comprises a plasma-poor component.
 23. A plasmapheresis process, comprising:a. positioning a blood-processing bag containing whole blood in a centrifuge rotor so that red blood cells will travel along a short internal dimension of said blood-processing bag during centrifugal separation; b. rotating said centrifuge rotor to centrifugally separate the whole blood into a plasma-rich component and a plasma-poor component within said blood-processing bag; and, c. partially collapsing said blood-processing bag by applying pressure to an external surface thereof to thereby expel plasma-rich component from said blood-processing bag and into a receiver container located within said centrifuge rotor as said rotor is rotating.
 24. A plasmapheresis process, comprising:a. withdrawing whole blood from a donor; b. introducing withdrawn whole blood from said donor into a flexible blood processing bag; c. positioning said blood-processing bag in a processing chamber within a centrifuge rotor, said processing chamber being contoured to support said blood-processing bag in a position whereby centrifugal separation can occur along a short internal bag dimension as said rotor is rotated; d. rotating said centrifuge rotor to centrifugally separate whole blood contained within said blood-processing bag into a plasma-rich component and a plasma-poor component; e. expelling plasma-rich component from said blood-processing bag and into a rceiver container located within said centrifuge rotor as it rotates; f. braking said rotor to a stop and expelling plasma-poor component from said blood-processing bag; g. returning plasma-poor component to said donor; and, h. optionally, repeating steps (a)-(g).
 25. In a pair of contoured support shoes for supporting a flexible blood processing bag formed from planar front and back surfaces sealed together around their edges in a centrifuge rotor:the improvement wherein said support shoes have inner surfaces having a general arc-shape to provide an annular, arcuate processing chamber and also having on one inner surface thereof a gentle slope from its top and bottom towards a horizontal center line and a gentle slope from both sides towards a vertical center line thereby providing a centrifugal slope from all points towards the center of said one inner surface.
 26. In a centrifuge system wherein a flexible blood-processing bag is supported between contoured shoes within a centrifuge rotor:the improvement wherein the radially inner contoured support surface has a greater slope at its upper portion than at its lower portion to provide for more efficient emptying thereof.
 27. Apparatus for centrifugally separating blood contained within a flexible blood processing bag into a first blood component and a second blood component, comprising:a. means for mounting said blood processing bag in a centrifuge rotor in a position so that the second blood component will be forced radially outward during centrifugal separation for a distance corresponding to a short internal bag dimension; b. means for rotating said centrifuge rotor at a speed sufficient to cause said second blood component to travel radially outwards along the short internal bag dimension thereby causing first blood component to collect near the radially inner surface of said bag; and, c. means for partially collapsing said blood processing bag by applying pressure to an external surface thereof to thereby expel first blood component from said blood processing bag and into a receiver container within said centrifuge rotor. 